We seek to understand protein and cofactor conformational and chemical dynamics through the design and synthesis of peptides and small proteins. This work should provide a fundamental framework for understanding a variety of kinetic phenomena ranging from the folding and misfolding of proteins to the structural and dynamic bases for the function of redox enzymes. As a part of a program project, we strive to develop synthetic and computational methods that can be use across the entire program, and we also apply these methods to study protein hydration, folding, and design. In particular, our aims are as follows: 1) We will develop temperature-dependent isotope-edited IR spectroscopy as a method to monitor conformational change, and apply it to determine the nanosecond to microsecond events in protein folding. 2) We will synthesize nitrile-containing amino acids and examine their utility as environment-sensitive probes of protein-protein interactions, protein folding, and protein membrane interactions. 3) We will design proteins that bind a variety of hemes, porphyrins, and other synthetic cofactors, and determine the functional properties and structures of these proteins.